- Intermolecular contacts in the crystal structures of specifically varied halogen and protonic group substituted azines
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A series of azines featuring differently halogen and protic group substituted pyridine, pyrimidine and pyridazine compounds have been synthesized and studied in terms of their crystal structures in order to develop a better understanding of the links between structural conditions and molecular packing behavior. Complemented by the structure results of related compounds known from the literature, intermolecular contact relationships connected to the present substance types were found, having potential use in future crystal engineering of similar compounds. This primarily involves the formation of N?I contacts aside from specific halogen?halogen and hydrogen bond type interactions.
- Hübscher, J?rg,Seichter, Wilhelm,Weber, Edwin
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- One-Pot and Two-Chamber Methodologies for Using Acetylene Surrogates in the Synthesis of Pyridazines and Their D-Labeled Derivatives
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Acetylene surrogates are efficient tools in modern organic chemistry with largely unexplored potential in the construction of heterocyclic cores. Two novel synthetic paths to 3,6-disubstituted pyridazines were proposed using readily available acetylene surrogates through flexible C2 unit installation procedures in a common reaction space mode (one-pot) and distributed reaction space mode (two-chamber): (1) an interaction of 1,2,4,5-tetrazine and its acceptor-functionalized derivatives with a CaC2?H2O mixture performed in a two-chamber reactor led to the corresponding pyridazines in quantitative yields; (2) [4+2] cycloaddition of 1,2,4,5-tetrazines to benzyl vinyl ether can be considered a universal synthetic path to a wide range of pyridazines. Replacing water with D2O and vinyl ether with its trideuterated analog in the developed procedures, a range of 4,5-dideuteropyridazines of 95–99% deuteration degree was synthesized for the first time. Quantum chemical modeling allowed to quantify the substituent effect in both synthetic pathways.
- Ananikov, Valentine P.,Ledovskaya, Maria S.,Polynski, Mikhail V.
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- Polymorph-specific chlorination of maleic-hydrazide
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The reaction of chlorination of maleic-hydrazide (1) with POC13 is specific to the substrate polymorph. Chlorination of either the triclinic polymorph of maleic-hydrazide (1), denoted MH1, or the monoclinic polymorph MH2 leads to a single product of 3,6-dichloropyridazine (2), while chlorination of the monoclinic polymorph MH3 under the same conditions results in two products: 3,6-dichloropyridazine (2) and 6-chloro-3-pyridazinone (3). The structural differences between polymorphs and their topochemical chlorination in phosphorus oxychloride are discussed. The crystal structure of 6-chloro-3-pyridazinone (3) monohydrate, determined in this study by X-ray diffraction, is built of ribbons of hydrogen-bonded 3 and water molecules. It has been established that the chlorination of ground crystals of polymorph MH3 yields exclusively the dichloropyridazine, which suggests that the crystal habit of MH3, the size of crystallites and the lower solubility of MH3 than MH1 and MH2 are the main reasons for the different course of the reaction.
- Katrusiak, Andrzej,Katrusiak, Anna
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- Synthesis and herbicidal evaluation of 3-N-substituted amino-6-benzyloxypyridazine derivatives
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A variety of 3-N-substituted amino-6-benzyloxypyridazine derivatives were designed and synthesized in satisfactory yields. Their structures were confirmed by IR, 1H-NMR, and elemental analysis; compound 5j was further determined by X-ray diffraction crystallography. Their herbicidal activities were evaluated through barnyard grass and rape cup tests in laboratory bioassays. Most of the title compounds 5 displayed moderate herbicidal activities against the dicotyledonous plant Brassica campestris L. The most active compounds in the laboratory were also evaluated in the greenhouse.
- Zhang, Min,Hu, Fang-Zhong,Zhao, Ting,Yang, Liu-Qing,Yang, Hua-Zheng
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- Pyridazine N-Oxides as Photoactivatable Surrogates for Reactive Oxygen Species
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A method for the photoinduced evolution of atomic oxygen from pyridazine N-oxides was developed. This underexplored oxygen allotrope mediates arene C-H oxidation within complex, polyfunctional molecules. A water-soluble pyridazine N-oxide was also developed and shown to promote photoinduced DNA cleavage in aqueous solution. Taken together, these studies highlight the utility of pyridazine N-oxides as photoactivatable O(3P) precursors for applications in organic synthesis and chemical biology.
- Basistyi, Vitalii S.,Frederich, James H.
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supporting information
p. 1907 - 1912
(2022/03/27)
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- Deaminative chlorination of aminoheterocycles
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Selective modification of heteroatom-containing aromatic structures is in high demand as it permits rapid evaluation of molecular complexity in advanced intermediates. Inspired by the selectivity of deaminases in nature, herein we present a simple methodology that enables the NH2 groups in aminoheterocycles to be conceived as masked modification handles. With the aid of a simple pyrylium reagent and a cheap chloride source, C(sp2)?NH2 can be converted into C(sp2)?Cl bonds. The method is characterized by its wide functional group tolerance and substrate scope, allowing the modification of >20 different classes of heteroaromatic motifs (five- and six-membered heterocycles), bearing numerous sensitive motifs. The facile conversion of NH2 into Cl in a late-stage fashion enables practitioners to apply Sandmeyer- and Vilsmeier-type transforms without the burden of explosive and unsafe diazonium salts, stoichiometric transition metals or highly oxidizing and unselective chlorinating agents. [Figure not available: see fulltext.]
- Ghiazza, Clément,Faber, Teresa,Gómez-Palomino, Alejandro,Cornella, Josep
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- Preparation method of 3, 6-dichloropyridazine
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The invention belongs to the technical field of medicines, and particularly relates to a preparation method of 3, 6-dichloropyridazine. The preparation method comprises the following steps: carrying out chlorination reaction on 3, 6-dihydroxypyridazine and N-chlorosuccinimide to generate 3, 6-dichloropyridazine; the chlorination reaction route is as follows: the method solves the technical problems of large environmental pollution, high process risk and high cost due to the adoption of the traditional chlorinating agent in the existing 3, 6-dichloropyridazine preparation method.
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Paragraph 0034-0039
(2021/04/14)
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- Efficient Phosphorus-Free Chlorination of Hydroxy Aza-Arenes and Their Application in One-Pot Pharmaceutical Synthesis
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The chlorination of hydroxy aza-arenes with bis(trichloromethyl) carbonate (BTC) and SOCl2 has been effectively performed by refluxing with 5 wt % 4-dimethylaminopyridine (DMAP) as a catalyst. Various substrates are chlorinated with high yields. The obtained chlorinated aza-arenes can be used directly with simple workup for succedent one-pot synthesis on a large scale.
- Wang, Jian,Li, Yan-Hui,Pan, Song-Cheng,Li, Ming-Fang,Du, Wenting,Yin, Hong,Li, Jing-Hua
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supporting information
p. 146 - 153
(2020/03/10)
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- AMINOIMIDAZOPYRIDINES AS KINASE INHIBITORS
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Compounds having formula (I), and enantiomers, and diastereomers, stereoisomers, pharmaceutically-acceptable salts thereof, (I) are useful as kinase modulators, including RIPK1 modulation. All the variables are as defined herein.
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Page/Page column 90
(2019/05/22)
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- Preparation method of chloro-substituted polyhydroxy aza-aromatic ring compound (by machine translation)
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The invention discloses a preparation method, namely BTC and SOCl, of a chloropolyhydroxyl aza heteroaromatic ring compound as a raw material with a polyhydroxy aza heteroaromatic ring compound as a raw material, and a preparation method thereof. 2 As the double chlorination reagent, a chloropolyhydroxyl aza-aromatic ring compound is produced by chlorination reaction with 4 - dimethylaminopyridine (DMAP) as a catalyst at room temperature to reflux temperature of the reaction, as a catalyst. BTC TC TC TC2 /DMDMAP chlorination system has high efficiency, high selectivity and chlorine substitution on a polyhydroxy nitrogen heterocyclic compound; the system can replace POCl3 , The production of phosphorus-containing wastewater is avoided. Using BTC as a chlorination reagent, the reaction by-product was HCl and CO. 2 . From the aspects of industrial wastewater treatment, environmental protection and the like, the advantages thereof are obvious; SOCl is distilled off after the reaction is ended. 2 The quantity is almost no loss, can be used repeatedly, and reduces the process cost. (by machine translation)
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Paragraph 0019; 0020; 0021-0024
(2019/10/01)
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- Synthesis and the interaction of 2-(1H-pyrazol-4-yl)-1H-imidazo[4,5-f][1,10]phenanthrolines with telomeric DNA as lung cancer inhibitors
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A novel series of 2-(1H-pyrazol-4-yl)-1H-imidazo[4,5-f][1,10]phenanthrolines were designed, synthesized and evaluated for their antitumor activity against lung adenocarcinoma by CCK-8 assay, electrophoretic mobility shift assay (EMSA), UV-melting study, wound healing assay and docking study. These compounds showed good inhibitory activities against lung adenocarcinoma. Especially compound 12c exhibited potential antiproliferative activity against A549?cell line with the half maximal inhibitory concentration (IC50) value of 1.48?μM, which was a more potent inhibitor than cisplatin (IC50?=?12.08?μM) and leading compound 2 (IC50?=?1.69?μM), and the maximum cell inhibitory rate being up to 98.40%. Moreover, further experiments demonstrated that compounds 12a–d can strongly interact with telomeric DNA to stabilize G-quadruplex DNA with increased ΔTm values from 12.44 to 20.54?°C at a ratio of DNA to compound 1:10. These results implied that growth inhibition of A549?cells mediated by these phenanthroline derivatives is possibly positively correlated to the fact their interaction with telomeric G-quadruplexs.
- Liu, Jiachun,Chen, Mei,Wang, Yanli,Zhao, Xiaoyin,Wang, Sijia,Wu, Yanling,Zhang, Wen
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- Design, synthesis, and bioactivity study of novel benzoylpyridazyl ureas
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A series of novel benzoylpyridazyl ureas were designed and synthesized from maleic anhydride and hydrazine monohydrate. These benzoylureas were identified by 1H NMR spectroscopy and element analysis. The bioactivities of the new compounds were evaluated. These compounds exhibited larvicidal activities against oriental armyworm, and in particular, compound 13 displayed comparable activity to the commercial insecticide Hexaflumuron. Most of these compounds also had some larvicidal activities against mosquito. Interestingly, some compounds showed good plant growth regulatory activities.
- Ranfeng,Zhang, Yonglin,Fuchun,Wang, Qingmin
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experimental part
p. 6356 - 6361
(2010/07/05)
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- Sulfonyl pyridazinone compounds useful as aldose reductase inhibitors
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This invention relates to novel sulfonyl pyridazinone compounds useful as aldose reductase inhibitors in the treatment or prevention of certain complications arising from diabetes mellitus, pharmaceutical compositions comprising the sulfonyl pyridazinone, pharmaceutical compositions comprising a combination of the sulfonyl pyridazinone together with a second pharmaceutical agent, therapeutic methods comprising the administration of the sulfonyl pyridazinone compounds, therapeutic methods comprising the administration of the sulfonyl pyridazinone compounds in combination with a second pharmaceutical agent and compounds useful as intermediates for preparing the sulfonyl pyridazinone compounds of this invention.
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- Therapies for tissue damage resulting from ischemia
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This invention relates to therapeutic methods for treatment or prevention of tissue damage resulting from ischemia in mammals.
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- Dramatically enhanced fluorescence of heteroaromatic chromophores upon insertion as spacers into oligo(triacetylene)s
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In continuation of a previous study on the modulation of π-electron conjugation of oligo(triacetylene)s by insertion of central hetero-spacer fragments between two (E)-hex-3-ene-1,5-diyne ((E)-1,2-diethynylethene, DEE) moieties (Fig. 1), a new series of trimeric hybrid oligomers (14-18 and 22-24, Fig. 2) were prepared (Schemes 1-3). Spacers used were both electron-deficient (quinoxaline-based heterocycles, pyridazine) and electron-rich (2,2′-bithiophene, 9,9-dioctyl-9H-fluorene) chromophores. With 19-21 (Scheme 4), a series of transition metal complexes was synthesized as potential precursors for nanoscale scaffolding based on both covalent acetylenic coupling and supramolecular assembly. The UV/VIS spectra (Fig. 3) revealed that the majority of spacers provided heterotrimers featuring extended π-electron delocalization. The new hybrid chromophores show a dramatically enhanced fluorescence compared with the DEE dimer 13 and homo-trimer 12 (Fig. 5). This increase in emission intensity appears as a general feature of these systems: even if the spacer molecule is non-fluorescent, the corresponding hetero-trimer may show a strong emission (Table 2). The redox properties of the new hybrid chromophores were determined by cyclic voltammetry (CV) and rotating-disk voltammetry (RDV) (Table 3 and Fig. 5). In each case, the first one-electron reduction step in the hetero-trimers appeared anodically shifted compared with DEE dimer 13 and homo-trimer 12. With larger spacer chromophore extending into two dimensions (as in 14-18, Fig. 2), the anodic shift (by 240-490 mV, Table 3) seems to originate from inductive effects of the two strongly electron-accepting DEE substituents rather than from extended π-electron conjugation along the oligomeric backbone, as had previously been observed for DEE-substituted porphyrins.
- Edelmann, Michael J.,Raimundo, Jean-Manuel,Utesch, Nils F.,Diederich, Francois,Boudon, Corinne,Gisselbrecht, Jean-Paul,Gross, Maurice
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p. 2195 - 2213
(2007/10/03)
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- Sulfonyl pyridazinone compounds as therapeutic agents for ischemic tissue damage
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This invention relates to therapeutic methods for treatment or prevention of tissue damage resulting from ischemia in mammals.
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- Synthesis of some 3,6-disubstituted pyridazines
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Some novel 3-halo-6-(4-substituted-phenoxy)pyridazines and 3,6-di-(4- substituted-phenoxy)pyridazines were synthesized from 3,6-dichloropyridazine or 3,6-diiodopyridazine. 3,6-Diiodopyridazine was prepared from 3,6- dichloropyridazine using hydriodic acid/iodine monochloride.
- Shin, Mi-Seon,Kang, Young-Jin,Chung, Hyun-A.,Park, Jung-Won,Kweon, Deok-Heon,Lee, Woo Song,Yoon, Yong-Jin,Kim, Sung-Kyu
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p. 1135 - 1142
(2007/10/03)
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- Selective deoxygenation of heteroaromatic N-oxides with olefins catalyzed by ruthenium porphyrin
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A new convenient method of deoxygenation of heteroaromatic N-oxides is described. Ruthenium porphyrin was used as a catalyst and this method expressed high yields for o-substituted pyridine N-oxides, quinoline N-oxide derivatives, acridine N-oxide, etc. under mild conditions. Moreover, nitro-, benzyloxy-, and ketone carbonyl groups, which can be affected by the usual deoxygenation methods such as catalytic hydrogenation or borane reduction, were retained.
- Nakagawa, Hiroshi,Higuchi, Tsunehiko,Kikuchi, Kazuya,Urano, Yasuteru,Nagano, Tetsuo
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p. 1656 - 1657
(2007/10/03)
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- Synthesis and Structure-Activity Relationships of Series of Aminopyridazine Derivatives of γ-Aminobutyric Acid Acting as Selective GABA-A Antagonists
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We have recently shown that an aryloaminopyridazine derivarive of GABA, SR 95103 , is a selective and competitive GABA-A receptor antagonist.In order to further explore the structural requirements for GABA receptor affinity, we synthesized a series of 38 compounds by attaching various pyridazinic structures to GABA or GABA-like side chains.Most of the compounds displaced GABA from rat brain membranes.All the active compounds antagonized the GABA-elicited enhancement of diazepam binding, strongly suggesting that all these compounds are GABA-A receptor antagonists.None of the compounds that displaced GABA from rat brain membranes interacted with other GABA recognition sites (GABA-B receptor, GABA uptake binding site, glutamate decarboxylase, GABA-transaminase).They did not interact with the Cl- ionophore associated with the GABA-A receptor and did not interact with the benzodiazepine, strychnine, and glutamate binding sites.Thus these compounds appear to be specific GABA-A receptor antagonists.In terms of structure-activity, it can be concluded that a GABA moiety bearing a positive charge is necessary for optimal GABA-A receptor recognition.Additional binding sites are tolerated only if they are part of a charge-delocalized amidinic or guanidinic system.If this delocalization is achieved by linking a butyric acid moiety to the N(2) nitrogen of a 3-aminopyridazine, GABA-antagonistic character is produced.The highest potency (ca.250 times bicuculline) was observed when an aromatic ? system, bearing electron-donating substituents, was present on the 6-position of the pyridazine ring.
- Wermuth, Camille-Georges,Bourguignon, Jean-Jacques,Schlewer, Gilbert,Gies, Jean-Pierre,Schoenfelder, Angele,et al.
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p. 239 - 249
(2007/10/02)
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- The Mechanism of Thermal Eliminations. Part 18. Relative Rates of Pyrolysis of 2-Ethoxypyrazine, 3-Ethoxypyridazine, 2-and 4-Ethoxypyrimidine, 3-Chloro-6-ethoxypyridazine, and 2-Chloro-4-ethoxypyrimidine : the Effect of the Aza 'Substituent' and ?-Bond Order on the Elimination Rate
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A kinetic study has been made of the first-order thermal decomposition of the title compounds into ethylene and the corresponding aza-substituted pyridines, between 650 and 713 K.The relative elimination rates at 650 K are (2-ethoxypyridine = 1): 0.545, 10.0, 1.03, 1.12, 9.68, and 3.28, respectively.The electronic effects of the aza 'substituent' are small, and a more important factor appears to be the C-N ?-bond order; this latter accounts for the high reactivity of the pyridazines.The effects of the chloro substituent and of the aza 'substituent' are explicable in terms of a balance between electron withdrawal from the C-O bond (producing deactivation) and from the nitrogen involved in the cyclic transition state (producing deactivation).The effects of the chloro substituents confirm that the most important step of the reaction is breaking of the C-O bond.The statistically corrected rate (per ring nitrogen) of 2-ethoxypyrimidine is unexpectedly low.This may reflect difficulty in achieving the coplanar transition state in which the lone pairs in the s-orbitals of oxygen and the nitrogen not involved in the elimination are brought into close proximity.
- Al-Awadi, Nouria,Taylor, Roger
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p. 1255 - 1258
(2007/10/02)
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- 7-[α-(2-Aminomethyl-1-cyclohexenyl)-acetamido]-3-heterocyclic thiomethyl-3-cephem-4-carboxylic acids
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7-[α-(2-Aminomethyl-1-cyclohexyl)-acetamido]-3-heterocyclic thiomethyl-3-cephem-4-carboxylic acids, and their nontoxic, pharmaceutically acceptable salts and their Schiff bases, as made by reaction of salicylaldehyde with the free amino group, are valuable as antibacterial agents and are particularly valuable as therapeutic agents in poultry and animals, including man, in the treatment of infectious diseases caused by many Gram-positive and Gram-negative bacteria.
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